QJM Advance Access originally published online on January 7, 2008
QJM 2008 101(2):164-166; doi:10.1093/qjmed/hcm154
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Oliguric acute renal failure following oral valacyclovir therapy
Sir,A 73-year-old Japanese man was admitted because of anuria, systemic edema and renal dysfunction. He had cardiac dysfunction due to dilated cardiomyopathy and had been treated with an angiotensin II receptor antagonist (ARB) and a beta-blocker for three years. He also had chronic kidney disease (CKD, stage III): his serum creatinine concentration, 104.3 µmol/l; estimated creatinine clearance (CrCl) (Cockcroft–Gault equation, 51.2 ml/min); and estimated glomerular filtration rate (eGFR) (MDRD equation modified by a Japanese coefficient,1 45.8 ml/min/1.73 m2), at one month previous to admission. Five days previous to admission, he was diagnosed to have varicella zoster and started to have oral valacyclovir 1 g three times a day and a non-steroidal anti-inflammatory drug (NSAID). Next day, he had noticed anuria and stopped to take valacyclovir and NSAID, but his anuria had not improved for three days. On admission, he was alert and had mild systemic edema, but blood pressure and body temperature were normal. Full blood count revealed mild anemia with normal peripheral blood smear, eosinophil counts and coagulation screen. He showed normal liver biochemistry including creatine kinase, but marked renal dysfunction (urea nitrogen, 16.4 mmol/l; creatinine, 600.2 µmol/l). Abdominal-computed tomography showed no remarkable abnormalities. As he showed anuria and marked renal dysfunction with a history of cardiac dysfunction, intermittent hemodialysis was immediately initiated and ARB was discontinued. On day 2, after the second session of hemodialysis, his urinary volume dramatically increased; thus, hemodialysis could be stopped. A drug lymphocyte stimulating test with valacyclovir was negative, but a plasma concentration of acyclovir, a metabolite of valacyclovir, on admission was markedly elevated [27.84 µg/ml; acyclovir maximum concentration after single dose administration of 1.0 g of valacyclovir to 8 healthy volunteers, 5.65 µg/ml ± 2.37 (mean ± SD)].2 His renal function gradually improved, ARB was restarted, and he was discharged on day 18, with creatinine concentration of 130.8 µmol/l and urea nitrogen of 6.8 mmol/l.
Acute renal failure in the present case is thought to be related with valacyclovir because oliguria occurred soon after the initiation of valacyclovir. Valacyclovir, L-valyl ester of acyclovir, is generally used as an anti-viral drug against herpes simplex viruses and varicella zoster virus.2 Renal dysfunction and central nervous system symptoms possibly develop when the patients have received inappropriately high doses of valacyclovir; thus, appropriate dose reduction of valacyclovir is required particularly in elderly patients and those with preexisting impaired renal function.2,3 In the present case, estimated CrCl and eGFR were 51.2 ml/min and 45.8 ml/min/1.73 m2, respectively, and our patient was appropriately dosed at 1 g three times a day, according to the prescribing information2: the dosages for varicella zoster patients with renal impairment: CrCl 
50 ml/min, 1 g every 8 h; CrCl 30–49 ml/min, 1 g every 12 h; CrCl 10–29 ml/min, 1 g every 24 h and CrCl < 10 ml/min, 0.5 g every 24 h; thus, the Cockcroft–Gault equation, the traditional method of estimating CrCl, might not be appropriate for valacyclovir dosing. Furthermore, Santons et al.4 described that acyclovir can increase total renal vascular resistance and reduce glomerular ultrafiltration coefficient, resulting in reducing GFR. Our patient was complicated with CKD and treated with ARB and NSAID, which are also known to disturb glomerular hemodynamics; thus, the marked reduction of GFR might have occurred even with the appropriate dosage of oral valacyclovir, resulting in oliguric acute renal failure. Therefore, the prompt reduction of plasma concentrations of acyclovir with hemodialysis might have improved glomerular hemodynamics and oliguria in the present case. Our study indicates that physicians should cautiously prescribe valacyclovir when patients with CKD, particularly treated with renin–angiotensin system inhibitors or NSAIDs, are seen.
Department of Internal Medicine
Shiga University of Medical Science
Otsu
Shiga, 520-2192
Japan
e-mail: toshiro{at}belle.shiga-med.ac.jp
Hemodialysis Unit
Shiga University of Medical Science
Otsu
Shiga, 520-2192
Japan
References
1. Imai E, Horio M, Nitta K, Yamagata K, Iseki K, Hara S, Ura N, Kiyohara Y, Hirakata H, Watanabe T, Moriyama T, Ando Y, Inaguma D, Narita I, Iso H, Wakai K, Yasuda Y, Tsukamoto Y, Ito S, Makino H, Hishida A, Matsuo S. Estimation of glomerular filtration rate by the MDRD equation modified for Japanese patients with chronic kidney disease. Clin Exp Nephrol (2007) 11:41–50.[CrossRef][Medline]
2. GlaxoSmithKline Prescribe information of VALTREXR 2006 July.
3. Carlon R, Possamai C, Corbanece U. Acute renal failure and severe neurotoxicity following valacyclovir. Intensive Care Med (2005) 31:1593.[CrossRef][Web of Science][Medline]
4. Santos MFF, Santos OFP, Boim MA, Razvickas CV, de Moura LA, Ajzen H, Schor N. Nephrotoxicity of acyclovir and gancyclovir in rats. Evaluation of glomerular hemodynamics. J Am Soc Nephrol (1997) 8:361–7.[Abstract]
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